otolaryngology-2019-posters-abstracts

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Otolaryngology 2019

Otolaryngology Online Journal | ISSN: 2250-0359 | Volume 9

July 18-19, 2019 | Valencia, Spain

OF EXCELLENCE

IN INTERNATIONAL

MEETINGS

YEARS

OTOLARYNGOLOGY: ENT SURGERY

Global Summit on

Otolaryngology Online Journal 2019, Volume 9

PASIREOTIDE, A SOMATOSTATIN ANALOGUE AS NOVEL TREATMENT FOR HEARING

LOSS

Vesna Petkovic, Krystsina Kucharava, Marijana Sekulic, Lukas Horvath

and

Daniel Bodmer

University of Basel, Switzerland

ensory hair cells in the inner ear are the primary receptors of auditory signals and hair cells degeneration is

the primary event in most cases of hearing loss. Gentamicin is a widely used antibiotic for the treatment of

gram-negative bacterial infections; although, its use often results in significant and permanent hearing loss.

Strategies to overcome the apparently irreversible loss of hair cells in mammals are crucial for hearing protec-

tion. Here author report that the somatostatin analogue pasireotide protects mouse cochlear hair cells from

gentamicin damage using a well-established

in vitro

gentamicin-induced hair cell loss model, and that the

otoprotective effects of pasireotide are due to Akt up-regulation via PI3K-Akt signal pathway activation. They

demonstrate active caspase signal in Organ of Corti explants exposed to gentamicin and show that pasireotide

treatment activates survival genes, reduces caspase signal and increases hair cell survival. The neuropeptide

somatostatin and its selective analogues have provided neuroprotection by activating five somatostatin re-

ceptor (SSTR1-SSTR5) subtypes. Pasireotide has high affinity for SSTR2 and SSTR5 and addition of SSTR2- and

SSTR5-specific antagonists lead to a loss of protection. The otoprotective effects of pasireotide were also ob-

served in a gentamicin-injured animal model.

In vivo

studies showed that 13 days of subcutaneous pasireotide

application prevents gentamicin-induced hair cell death and permanent hearing loss in mice. Auditory brain-

stem response analysis confirmed the protective effect of pasireotide, and they found a significant threshold

shift at all measured frequencies (4, 8, 16, 24 and 32 kHz). Together, these findings indicate that pasireotide is

a novel otoprotective peptide acting via the PI3K-Akt pathway and may be of therapeutic value for hair cell

protection from ototoxic insults.